Endothelial dysfunction is a critical determinant of many chronic diseases including cardiovascular and kidney disease. Endothelial dysfunction is defined by a loss of NO bioavailability and increased reactive oxygen species (ROS). Previous reports show that mitochondrial-derived ROS (mtROS) is a major source of ROS in endothelial cells. Endothelial senescence and apoptosis are regulated by mtROS and changes in mitochondrial gene expression. Histone deacetylases (HDACs) remove acetyl groups from histones epigenetically regulating gene transcription via deacetylation of histone proteins or post-translation deacetylation of non-histone proteins. We previously presented that increased HDAC1, a class I HDAC, expression reduces NO production and increases maximum respiratory oxygen consumption rate in endothelial cells. Reports also show HDACs function as gene silencers or activators. We hypothesized that increased HDAC1 expression in endothelial cells leads to increased mtROS and mitochondrial dysfunction via increased expression of key mitochondrial genes. Bovine aortic endothelial cells (BAECs) were transiently transfected with HDAC1. BAECs were then evaluated for mtROS by mitoSox fluorescence and mRNA expression of key mitochondrial regulatory genes, NRF2, TFAM, and PGC1a, by RT-PCR. MitoSox fluorescence was increased in cells with HDAC1 OE as compared to vehicle transfections. Gene expression of TFAM was significantly increased (p=0.0367; n=5); NRF2 expression trended up (p=0.0746; n=5); and, PGC1a expression remained unchanged (p=0.9952; n=5) as compared to vehicle transfections (n=6). These results suggest increased HDAC1 in endothelial cells may lead to increased mtROS and alterations in mitochondrial function.